Lithium Found Superior to Other Mood Stabilizers in Improving Outcomes in Youth With Bipolar Disorder

Youth with bipolar disorder who take lithium may be less likely to attempt suicide than those who take other mood stabilizers, according to a study in the Journal of the American Academy of Child & Adolescent Psychiatry. The study also found that these youth have fewer depressive symptoms and better psychosocial function compared with those not taking lithium.

These findings are similar to those found in previous studies of adults with bipolar disorder, “showing that lithium might improve mood course (including depressive symptoms), prevent suicide attempts, and ameliorate aggression,” wrote Danella M. Hafeman, M.D., Ph.D., of the University of Pittsburgh and colleagues. “When considering optimal treatment for [bipolar disorder] in youth, these potential benefits should be weighed against the possible risks of long-term lithium exposure (e.g., effects on kidney and thyroid function) and the fact that [lithium] can be lethal in overdose.”

Hafeman and colleagues analyzed longitudinal data collected from the Course and Outcome of Bipolar Youth (COBY) study, which included 413 youth aged 7 to 17 who met criteria for DSM-IV bipolar spectrum disorders. As part of the COBY study, the researchers followed up with youth every six months for four years, tracking the medications they took (the participants reported the medication they took, not what they were prescribed); suicidal ideation and attempts; and fluctuations in mood, anxiety, substance use, and psychosocial function. During follow-ups, parents were asked to fill out a form that asked about the participant’s aggression and other externalizing behaviors.

Hafeman and colleagues relied on data collected from 340 youth during 2,638 follow-ups to assess whether the youth who took lithium differed on these measures compared with those who took antimanic anticonvulsants, first- and second-generation antipsychotics, and/or lamotrigine. The researchers found that youth in the lithium group had half as many suicide attempts, fewer depressive symptoms, less psychosocial impairment, and less aggression than those taking other mood-stabilizing medications.

The researchers acknowledged several limitations of the study, including a lack of information on medication adherence, side effects, and/or tolerability.

“Despite these limitations, the COBY study provides a unique opportunity to assess the effect of medications in a larger sample, with much longer follow-up, and arguably more generalizable to [this] patient population than [a randomized, controlled trial],” Hafeman and colleagues wrote. “Future work should focus on elucidating the mechanisms by which [lithium] improves outcomes in [youth with bipolar disorder], so that novel therapeutics can be developed to target these mechanisms with fewer side effects; and identifying who will best respond to [lithium]…”

For more on the COBY study, see the American Journal of Psychiatry article “Four-Year Longitudinal Course of Children and Adolescents With Bipolar Spectrum Disorders: The Course and Outcome of Bipolar Youth (COBY) Study.”

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Wraparound Services Increase Benefits of Mental Health Courts, Study Finds

A program that offers integrated behavioral-health and criminal-justice services to individuals who are participating in mental health courts may help reduce recidivism and promote recovery among participants, a pilot study published in Psychiatric Services in Advance suggests.

Mental health courts divert people with mental health and/or substance use disorders who have been arrested from jail to court-monitored treatment referral and support.

Debra A. Pinals, M.D., of the University of Michigan Medical School and colleagues evaluated the impact of an intervention called Maintaining Independence and Sobriety through Systems Integration, Outreach, and Networking–Criminal Justice (MISSION-CJ) on individuals involved in a Massachusetts mental health court. MISSION-CJ offers a series of wraparound services including case management, in-community support, structured group treatment sessions designed to simultaneously treat co-occurring mental health and substance use disorders, peer support, vocational and educational support, trauma-informed care, and frequent coordination with probation officers.

A total of 97 mental health court participants who were found guilty in criminal court and who met criteria for a DSM-IV-TR axis I psychiatric disorder (for example, depression) and reported current or past substance use were included in the study. The researchers evaluated the participants using the Addiction Severity Index, the Behavior and Symptom Identification Scale-32, and the PTSD Checklist–Civilian Version at the start of the study and again six months later.

Participants were primarily male with an average age of 34, had spent an average of five years incarcerated, and had an average 14-year history of illegal drug use; 91% had experienced depression. The researchers found that after six months in MISSION-CJ, participants experienced a significant reduction in nights incarcerated, illegal drug use, trauma symptoms, and behavioral health symptoms.

The researchers acknowledged several limitations of the study, including the small sample size and the lack of a comparison group who did not receive MISSION-CJ.

Nonetheless, they concluded, “[T]his pilot study demonstrates that the MISSION-CJ intervention could be offered to mental health court participants … alongside the mental health court, with promising preliminary results. … Future studies comparing the effectiveness and cost-effectiveness of MISSION-CJ, usual mental health court processes, and any alternative interventions are needed to address the needs of this growing population.”

For related information, see the Psychiatric Services article “Improving the Evaluation of Adult Mental Disorders in the Criminal Justice System With Computerized Adaptive Testing.”

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Blood Biomarkers May Help Identify Trauma Patients at Risk of Chronic PTSD

Analyzing blood samples from patients who have recently experienced trauma may predict those most likely to develop chronic posttraumatic stress disorder (PTSD), according to a study published today in AJP in Advance. Specifically, the study found that patients with low blood levels of the inflammatory molecules tumor necrosis factor α (TNFα) and interferon-γ (IFNγ) in the hours following trauma were more likely to develop chronic PTSD in the ensuing months.

“The findings suggest that assessing immunological changes in response to trauma exposure in the emergency department may help identify patients who are most at risk for developing chronic PTSD symptoms in the aftermath of trauma,” wrote Vasiliki Michopoulos, Ph.D., of Emory University School of Medicine and colleagues. “Such individuals may benefit from immediate psychological and pharmacological interventions that have been shown to be effective in attenuating PTSD development.” 

The study included 505 adults (aged 18 to 65) who were admitted to the emergency department at Atlanta’s Grady Memorial Hospital after experiencing a trauma. All the study patients received a baseline psychological exam and had blood drawn within a few hours of the traumatic incident; they then returned for follow-up assessments of PTSD symptoms one, three, six, and 12 months later. 

A total of 273 patients completed at least one follow-up visit and were included in the final analysis. Each patient was assigned to one of three groups, based on their PTSD symptoms at baseline and follow-up visits: those with chronic PTSD (n=28), those who developed PTSD but recovered (n=85), and those who did not develop PTSD (n=160). 

The researchers analyzed 27 different inflammatory and anti-inflammatory molecules from the patient blood samples obtained shortly after trauma and found that the patients with chronic PTSD had significantly lower blood levels of TNFα and IFNγ—both of which contribute to inflammation—compared with patients in the other two groups. Some previous research had suggested that anti-inflammatory molecules might promote PTSD resilience, but the investigators did not find any differences in anti-inflammatory biomarkers across the three groups. However, the authors noted that because they analyzed blood taken just hours after a trauma, there may be other molecules involved in PTSD risk or resilience at other time points. 

To read more about trauma-related biomarkers, see the Psychiatric News story “FDA Clears the Way for First Blood Test to Evaluate Head Injuries.” 

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Meta-Analysis Hints at Benefits of Repetitive TMS for Treating Substance Use

Using repetitive transcranial magnetic stimulation (rTMS) to target a brain region thought to play a role in decision-making and self-control may reduce cravings and substance use in people with alcohol, nicotine, and illicit drug dependence, a meta-analysis in Addiction has found. During treatment with rTMS, electromagnetic coils placed against the scalp deliver magnetic pulses to stimulate a portion of the brain. 

“Although an anti-craving effect of rTMS intervention has been indicated by previous literature, the effect of different rTMS protocols on craving and substance consumption and the association between stimulation parameters and effect sizes has not been systematically investigated,” Jack J.Q. Zhang, M.Sc., of The Hong Kong Polytechnic University and colleagues wrote. 

Zhang and colleagues analyzed data from 26 studies published between January 2000 and October 2018 to determine which ways of using rTMS yield the best results for curbing cravings and substance use. The studies involved 748 participants with alcohol, nicotine, or illicit drug dependence and compared the effect of active rTMS with sham (fake) stimulation. Participants reported their cravings and substance use via tools such as questionnaires at various points in the studies. 

They found that stimulation of the left dorsolateral prefrontal cortex (DLPFC), located toward the top left side of the brain, significantly reduced cravings in participants who received active treatment compared with those who received sham treatment. Treatment of the left DLPFC appeared to be more effective in reducing cravings in participants who were dependent on illicit drugs (such as cocaine and heroin), than in those with nicotine or alcohol dependence. rTMS of the right DLPFC had no significant effect on cravings in participants who received active treatment compared with those who received sham treatment.

Treatment involving stimulation of the left DLPFC reduced substance use in participants who received active treatment, as well. Treatments involving bilateral stimulation (both the left and right) of the DLPFC and another part of the brain called the insula also curbed substance use. 

The researchers noted that the positive effects of rTMS appeared to be short-lived and often wore off by follow-up (on average, four months later). 

“Our results … highlight the need to optimize intervention parameters and to increase the durability of the anti-craving and consumption-reducing effects [of rTMS],” they concluded.

For related news, see the Journal of Neuropsychiatry and Clinical Neurosciences article “Outcome of Non-Invasive Brain Stimulation in Substance Use Disorders: A Review of Randomized Sham-Controlled Clinical Trials.”

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Antidepressant Adherence Linked to Increased Survival in Patients With Cancer, Study Finds

A study published this week in Depression & Anxiety suggests that among patients with cancer who are prescribed antidepressants, those who take the medication may live longer than those who are nonadherent.

Patients with cancer are known to have higher rates of depression than the general public—a factor that may reduce adherence to cancer treatment and increase their risk of death. The findings “add to the pressing need to encourage adherence to [antidepressants] among cancer patients,” wrote Gal Shoval, M.D., of the Geha Mental Health Center in Tel Aviv, Israel, and colleagues.

To examine the relationship between antidepressant adherence and mortality in people with cancer, Shoval and colleagues analyzed the medical records of patients with cancer who had at least one prescription for an antidepressant between January 2008 and January 2012. Patients were followed from the time of initial antidepressant prescription until death or the end of the four-year study.

Patients were categorized into one of four adherence groups: Nonadherent if adherence was below 20%, poor adherence for those with 20% to 50% adherence, moderate adherence for those with 50% to 80% adherence, and good adherence for those with adherence above 80%. Of the 42,075 patients included in the analysis, 28.9% were nonadherent, 16.2% had poor adherence, 17.6% had moderate adherence, and 37.4% had good adherence.

The researchers found that greater adherence to antidepressants was associated with decreased risk of all‐cause mortality, after adjusting for age, sex, socioeconomic status, smoking status, and physical comorbidities. Compared with the nonadherent group, risk of death was 20% lower in those with good adherence, 23% lower in those with moderate adherence, and 11% lower in those with poor adherence. A subanalysis of patients with melanoma, breast, colon, lung, or prostate cancer found similar results by cancer type except for melanoma.

The researchers noted several limitations of the study, including the fact they did not have access to causes of death data.

“Our findings not only indicate that adherence to [antidepressants] is associated with increased survival in patients with cancer, but that this relationship may be to some extent continuous, that is, even partial adherence to [antidepressants] may be beneficial in terms of survival,” the authors wrote.

For related information, see the Psychiatric News article “Best Practices for Treating Cancer Patients With Psychiatric Symptoms.”

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Behavioral Activation Could Expand Treatment Options for Patients With PTSD

A form of cognitive-behavioral therapy known as “behavioral activation,” which focuses on engaging patients in activities that improve mood, may be a promising alternative treatment for patients with posttraumatic stress disorder (PTSD), according to a report published today in Psychiatric Services in Advance.

“Elements of behavioral activation are relatively straightforward and easy to implement in a range of health care settings by providers with varying backgrounds and training,” wrote Amy Wagner, Ph.D., of the Department of Veterans Affairs (VA), Portland Health Care System and colleagues. “[O]ur findings suggest that behavioral activation is a promising therapy that may expand the reach of PTSD treatment.”

Originally designed for depression, behavioral activation is based on the theory that as individuals become depressed, they tend to isolate and avoid activities they would normally enjoy, which may maintain or worsen their depressive symptoms. The goal of behavioral activation is to decrease avoidance and isolation and increase engagement in activities that have been shown to improve mood.

Wagner and colleagues randomized 80 Iraq and Afghanistan veterans with PTSD to either eight, 60-minute sessions of behavioral activation or standard treatment. Standard treatment included individual therapy (such as prolonged exposure therapy or cognitive processing therapy), group therapy, and/or pharmacotherapy.

In the eight-session protocol, the tenets of behavioral activation were adapted for PTSD. Sessions 1 and 2 focused on learning the treatment model, assessing and discussing PTSD avoidance and how it contributes to functional impairment, assessing values and goals, and identifying specific activities that will improve symptoms. Sessions 3 through 7 focused on assigning activation tasks, assessing the effects of activation, and promoting problem solving. The final session focused on reviewing progress, relapse prevention tactics, future activation targets, and additional treatment.

The researchers assessed PTSD symptoms using the Clinician-Administered PTSD Scale (CAPS) and depressive symptoms using the Beck Depression Inventory-II at baseline, 12 weeks, and 24 weeks.

Although both groups showed improvement over time on measures of PTSD (as measured by clinical interview and self-report), depression, and overall functioning, the behavioral activation group showed greater reductions on subjective measures of PTSD and depression relative to standard care, the authors noted.

“Behavioral activation may be a viable alternative treatment for PTSD for individuals who do not want or who are unable to access trauma processing therapy,” the researchers wrote. “With its focus on behavioral avoidance and increasing functionality, behavioral activation is also well-suited for the treatment of conditions commonly comorbid with PTSD, such as depression and chronic pain.”

For related news, see the Psychiatric Services article “Change in Patient Activation and Mental Illness Symptoms After Communication Training: A Multisite Study With a Diverse Patient Sample.”

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Borderline Symptoms at Age 12 Predict a Variety of Negative Outcomes at Age 18

Twelve-year-old children who exhibit symptoms associated with borderline personality disorder—such as experiencing extremes of rage, despair, or excitement—are at higher risk of having poor mental health by age 18, according to a report in the Journal of the American Academy of Child & Adolescent Psychiatry. The study also found these youth are more likely than their peers to be victims of violence and experience poor educational and employment outcomes.

Some mental health professionals are reluctant to diagnose borderline symptoms in young teenagers because it is regarded by some as a stigmatizing diagnosis, noted Jasmin Wertz, Ph.D., of the Department of Psychology and Neurosciences at Duke University and colleagues. “[O]ur findings argue in favor of early access to treatment for adolescents with borderline symptoms and against a ‘wait-and-see’ approach.”

A total of 2,232 British children in the Environmental Risk Longitudinal Twin Study (representing 1,116 families with same sex twins) were assessed during home visits at age 5, 7, 10, and 12; during these visits their mothers were also interviewed. At age 18, the participants were interviewed alone.

When the participants were 12, the researchers asked their mothers to rate how well a list of attributes described their children; the list included such statements as “easily jealous,” “emotions spiral out of control, has extremes of rage, despair, or excitement,” “angry and hostile,” and “engages in self-harm behavior.” Six years later, the researchers evaluated the participants for a variety of mental health disorders (including alcohol use disorder, conduct disorder, and depression) and asked them about history of suicide attempts and self-harm, academic and employment achievement, and experiences of victimization. This information was corroborated using reports by co-informants nominated by each twin (typically their co-twin and a parent) and official records.

Participants with more borderline symptoms at age 12 experienced worse mental health at age 18 compared with their peers with fewer symptoms: They were more likely to meet diagnostic criteria for a mental disorder, to have attempted suicide or engaged in self-harm, and to have used clinical and support services to cope with emotional and behavioral problems. They were also more likely to report experiencing of victimization during adolescence, performing poorly in school, and unemployment, the authors reported.

“Our findings show that adolescents’ borderline symptoms signal a longer-term need for care,” the researchers wrote. “Adolescents should be monitored and supported accordingly, particularly during the transition to adulthood when they face discharge from child and adolescent mental health services.”

For related information, see the Psychiatric News article “Experts Offer Guidance for Treating Patients With Borderline Personality Disorder” and the Psychiatric Services article “Treatment of Borderline Personality Disorder: Is Supply Adequate to Meet Public Health Needs?”

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Cannabis Use Before, During Pregnancy Rising, Study Finds

An analysis of medical records from pregnant women in northern California shows that cannabis use before and during pregnancy increased significantly over a nine-year period, according to a study in JAMA Network Open. The percentage of women who reported using cannabis in the year before becoming pregnant rose from 6.8% in 2009 to 12.5% in 2017, while the number of women who used cannabis while pregnant rose from nearly 2% to 3.4% during this period.

“Frequent cannabis use among pregnant women raises important public health concerns, as initial evidence suggests that heavier use might be associated with worse neonatal health outcomes,” wrote Kelly Young-Wolff, Ph.D., M.P.H., of Kaiser Permanente Research and colleagues. “Pregnant women who use cannabis more frequently during pregnancy are also more likely to use other drugs, and future research is critically needed to examine the short- and long-term health outcomes for mothers and their offspring associated specifically with daily [versus] occasional cannabis use during different time points in pregnancy.”

Young-Wolff and colleagues assessed Kaiser health records on 276,991 women who became pregnant between January 1, 2009, and December 31, 2017, and completed an assessment of their current and past cannabis use during their first prenatal visit. The final analysis included 367,403 pregnancies (75,234 women had more than one pregnancy during the study period).

The researchers found that the average number of women who reported daily, weekly, or monthly cannabis use during pregnancy or in the year prior increased between 2009 and 2017, with daily use rising the most rapidly. Between 2009 and 2017, the number of women who used cannabis daily in the year prior to pregnancy rose from 1.2% to 3.1%, while among pregnant women this number rose from 0.3% to 0.7%.

Younger women, black women, and women with lower average incomes were more likely to use cannabis before and during pregnancy.

Young-Wolff and colleagues noted that a previous analysis that confirmed prevalence of cannabis use during pregnancy using urine tests also reported increased use over time; this suggests that the current study findings are not simply the result of women being more willing to disclose their cannabis use due to wider social acceptance of the drug.

To read more about cannabis use, see the Psychiatric News article “Daily and High-Potency Use of Cannabis Linked to Psychosis.”

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ADHD Medications May Lower Risk of Unintentional Injuries in Children, Adolescents With ADHD

Medication for attention-deficit/hyperactivity disorder (ADHD) may help lower the risk of unintentional injuries in children and adolescents with ADHD, a study in the Journal of the American Academy of Child & Adolescent Psychiatry has found.

“[Prior studies] suggest that ADHD is associated with a 40% to 50% increase in the risk of injuries in children and adolescents. Pharmacological treatment for ADHD has been reported to be effective for core symptoms and cognitive deficits associated with ADHD. Hence it may be hypothesized that, by reducing distractibility, impulsivity, and overactivity, ADHD medication may prevent unintentional injuries,” Laura Ghirardi, M.Sc., of the Karolinska Institutet in Stockholm and colleagues wrote.

To test their hypotheses, the researchers analyzed prescription and health data from more than 1.9 million children and adolescents aged 6 to 19 years who had either been diagnosed with ADHD or received a prescription for ADHD medication between 2005 and 2014. They followed the participants for a median of 15 to 17 months and tracked emergency department visits for injuries with an unintentional cause, including traumatic brain injuries. During the follow-up period, 87,154 study participants had at least one emergency department visit for an unintentional injury.

The researchers found that participants who were taking ADHD medications (based on prescription claims data) were 13% to 15% less likely to have unintentional injuries during the follow-up period than participants who were not taking medications. They also found that participants who took ADHD medications were 9% to 15% less likely to have an unintentional traumatic brain injury than participants who did not take the medications.

The researchers also looked at how taking ADHD medications affected risk on an individual level (the difference in risk between taking the medication and not taking the medication in the same person). They found that participants were 29% less likely to have unintentional injuries and 33% to 37% less likely to experience traumatic brain injuries when they took ADHD medications than when they didn’t take the medications.

In their conclusion, the researchers noted that their results were similar for boys and girls at different ages.

“These results highlight how the use of ADHD medication may be associated with beneficial effects that go beyond reducing core symptoms of ADHD and extend to the prevention of health-adverse events, such as physical injuries, including [traumatic brain injury],” they wrote.

For related news, see the Psychiatric News article “Medicated ADHD Patients Have Reduced Risk of Motor Vehicle Crashes” and the Psychiatric Services article “Evidence of Low Adherence to Stimulant Medication Among Children and Youths With ADHD: An Electronic Health Records Study.”

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Family Involvement in Care of Hospitalized Psychiatric Patients May Boost Discharge Planning, Follow-up Care

Involving families and loved ones in care when psychiatric patients are hospitalized is associated with a greater likelihood of comprehensive discharge planning and follow-up care, a study in Psychiatric Services in Advance has found.

Morgan Haselden, M.P.H., of the New York State Psychiatric Institute and colleagues reviewed the records of 179 individuals hospitalized for a psychiatric condition in New York City in 2012 and 2013. They determined the involvement of family (including anyone close to the patient who provided support) in the patients’ care via documentation in the patients’ medical records of specific activities such as visiting with the patient or attending family therapy sessions. They also determined whether hospital staff had performed three discharge planning activities: communicating with an outpatient health care professional, scheduling a post-discharge mental health appointment for the patient, and forwarding a discharge summary to the provider the patient was scheduled to see. Finally, the researchers determined whether the patient had received follow-up care.

The researchers found that hospital staff were more than twice as likely to complete all three discharge activities for patients whose families visited them in the hospital, communicated with staff about services offered to families, or attended family meetings or therapy sessions than for those whose families did not engage in these activities. Patients were more than twice as likely to attend a mental health appointment within seven days of discharge if their families were contacted by hospital staff, communicated with hospital staff about the patient’s health or mental health, or discussed with staff the patient’s post-discharge treatment plan. Patients were more than three times as likely to attend a mental health appointment within 30 days of discharge if there had been any involvement between family and hospital staff.

“This finding lends support to the benefits of family involvement in mental health care and adds new evidence that these benefits extend to the psychiatric hospitalization setting,” the researchers wrote.

The researchers noted two caveats to their study. First, they stated that medical record documentation “should not be considered as fully representing actual activities and interactions, especially given the pace of inpatient care and the lack of uniform documentation standards.” Second, they noted that the findings may not be generalizable to rural settings because families in urban settings like New York City may live closer to hospitals or have greater access to transportation to visit patients.

The authors concluded, “Involvement of patients’ families is an inexpensive intervention, and although it is standard care for hospital staff to contact and involve families, such interactions do not always occur. Hospitals should formalize efforts to educate staff about the benefits of involving families in treatment and should implement standard procedures requiring contact and communication.”

For related information, see the Psychiatric Services article “Family Involvement in the Clinical Care of Clients With First-Episode Psychosis in the RAISE Connection Program.”

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Psychiatrists Describe Dangers in Physician ‘Burnout’ Becoming Catchall Term for Emotional Distress

Despite ongoing efforts by health care systems and professional medical organizations to create tools and practices to decrease physician burnout, physician depression and suicide prevention remain “relatively ignored,” wrote psychiatrists Maria A. Oquendo, M.D., Ph.D., Carol A. Bernstein, M.D., and Laurel E. S. Mayer, M.D., in an article appearing today in JAMA Psychiatry.

The authors described several factors that may contribute to the imbalance between attention paid to physician burnout versus major depressive disorder, including the ongoing stigma of mental illness and its treatment: “[T]he term burnout, which indicates a human reaction to something outside oneself, is less stigmatized [than major depressive disorder],” they wrote. This has allowed it “to become a catchall term for emotional distress experienced by physicians.”

Additionally, many symptoms of burnout overlap with symptoms of major depressive disorder (MDD), they noted. “The shifting definition of burnout, in concert with the overlap with psychiatric symptoms, sets the stage for a situation in which burnout can be invoked and a treatable diagnosis missed,” they wrote. “As a result, a physician dutifully completing a burnout screening inventory for self-evaluation, as now recommended by the Accreditation Council for Graduate Medical Education, could easily conclude that she or he has burnout rather than MDD.” Such missed opportunities may prevent or delay treatments, putting the physician in danger.

What can be done to resolve this problem? Oquendo, Bernstein, and Mayer suggested several solutions including screening physicians for depression, anxiety, and substance use disorders when screening for burnout and creating confidential and easily accessible psychiatric services for physicians and trainees.

“Ultimately, the biggest challenge is rolling back the corrosive effects of stigma so that more affected physicians will feel comfortable acknowledging, at least to themselves and their personal physician, that what ails them is a treatable brain disorder and not simply an impossible work situation,” the authors concluded.

Oquendo is a past APA president and a professor and chair of psychiatry at the Perelman School of Medicine at the University of Pennsylvania. Bernstein is a past APA president and vice chair for faculty development at Albert Einstein College of Medicine/Montefiore Medical Center. Mayer is an associate professor of clinical psychiatry at the Columbia University Vagelos College of Physicians and Surgeons.

For more on burnout, including a Psychiatric News series on this topic, see APA’s Well-being and Burnout Resources.

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Frequent Use of Medications for Sleep May Increase Dementia Risk, Especially Among Older White Adults

Frequent use of sleep medications appears to be associated with increased long-term risk of dementia, particularly among older white adults, according to research presented at the Alzheimer's Association International Conference in Los Angeles this week.

“Based on our findings, we recommend that clinicians make more effort to be aware of their patients’ sleep problems including use of sleep aids,” said lead study author Yue Leng, Ph.D., of the University of California, San Francisco, in a press release.

Leng and colleagues studied 3,068 black and white community-dwelling older adults aged 70 to 79 years who did not have dementia and were enrolled in the Health, Aging, and Body Composition study. At the beginning of the study, the participants were asked to rate their use of “sleeping pills or other medication” to help them sleep using the following responses: “never,” “rarely (once a month or less),” “sometimes (2 to 4 times per month),” “often (5 to 15 times per month),” or “almost always (16 to 30 times per month).”

A total of 147 (4.8%) participants reported taking sleep medications “sometimes,” and 172 (5.6%) reported “often” or “almost always.” A total of 34 black participants (2.7%) and 138 white participants (7.7%) reported taking sleep medications “often” or “almost always.”

The researchers tracked whether the participants experienced dementia over a 15-year period using hospital records and records of dementia medication use, as well changes in global cognition scores. After controlling for a variety of factors, including body mass index, depressive symptoms, physical activity, and APOE4 genotype, the researchers calculated the risk associated with sleep medication use. The researchers found that those who reported taking sleeping medication “often” or “almost always” were 43% more likely to develop dementia than those who reported “never” or “rarely” taking sleep medications. Whether the change in risk is due to the medications or sleep problems is not yet known, the researchers noted.

Additional analysis revealed that the increased dementia risk among the frequent users was observed only among the white participants (hazard ratio=1.79). There was no association between use of sleep medication and dementia in black participants (hazard ratio= 0.84). The association did not differ by sex.

“Further studies are needed to examine the cognitive effects of different types of sleep medications and to understand potential mechanisms,” the researchers wrote.

For related information, see the Psychiatric News article “Estimates of Adult Benzodiazepine Use Double.”

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Nabaximols Nasal Spray May Reduce Cannabis Use By Some Patients

A study published today in JAMA Internal Medicine reports that the cannabinoid agonist nabiximols can reduce cannabis use among people with cannabis dependence when combined with behavioral therapy. Nabiximols is a nasal spray composed of purified tetrahydrocannabinol (THC) and cannabidiol (CBD)—two of the primary active components of cannabis.

Study participants who received a combination of nabiximols and behavioral therapy reported using cannabis about 33% fewer days than those allocated to placebo and behavioral therapy, noted Nicholas Lintzeris, M.B.B.S., Ph.D., of Australia’s Drug and Alcohol Services and colleagues. “The reductions in illicit cannabis use and a safer route of administration … suggest the harm-reduction benefits of cannabinoid agonist treatment,” the authors wrote.

Lintzeris and colleagues enrolled 128 adults with cannabis dependence (as defined by the International Classification of Diseases, 10th Revision, or ICD-10) who were seeking treatment to participate in a 12-week trial. As part of the trial, the participants received either nabiximols or placebo nasal spray for daily use and were offered six individual cognitive-behavioral therapy sessions over the course of the trial. Each individual nabiximols spray contains 2.7 mg of THC and 2.5 mg of CBD, and participants could take up to 32 sprays daily.

At baseline, the participants reported using cannabis about 25 of the past 28 days. During the 12-week trial, adults in the placebo group reported significantly more days using cannabis (53 of 84 days) compared with those in the nabiximols group (35 of 84 days). Although there was no statistical difference between the groups in the number of participants who achieved cannabis abstinence (defined as at least 28 consecutive days without use), more adults in the nabiximols group were able to cut their cannabis use by 50% or more (54.1% vs. 28.9%).

The authors noted several limitations of the study, including the finding that only about half of the patients in the placebo and nabiximols groups stayed in treatment throughout the 12-week study. “Although our treatment retention of 46.9% at 12 weeks is comparable with prior randomized clinical trials of cannabinoid agonist treatment (55% at 11 weeks and 67% at 12 weeks), the limited treatment retention across these studies highlights the fact that cannabinoid agonist treatment is not effective for or acceptable to all patients,” Lintzeris and colleagues wrote. “Whereas nicotine-agonist and opioid-agonist treatments are considered frontline therapies, our findings suggest a more cautious approach for cannabinoid agonist treatment at this time.”

For related information, see the Psychiatric News article “Medications May Ease Cannabis Withdrawal But Fail to Achieve Abstinence” and the Psychiatric Services article “Thinking Carefully About Marijuana Legalization: Public Health Considerations for State Policy Makers.”

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Study Pinpoints Activities Associated With Reduced Risk of Cognitive Decline

Mentally stimulating activities like using a computer, playing games, crafting, and participating in social activities were associated with a lower risk of mild cognitive impairment in older people, a study published in Neurology has found. People with mild cognitive impairment, which is not the same as dementia, may have memory loss or have difficulty following conversations or understanding complex information.

Janina Krell-Roesch, Ph.D., of Mayo Clinic’s Translational Neuroscience and Aging Laboratory, and colleagues analyzed five-year data from 2,000 participants in the population-based Mayo Clinic Study of Aging. The participants were at least 70 years old at the beginning of the study, and none of them had mild cognitive impairment when they enrolled. Participants completed a questionnaire about how often they took part in five types of mentally stimulating activities during middle age (ages 50 to 65) and in later life (age 66 and older). The activities were reading books, crafting such as pottery or sewing, doing computer activities, playing games like cards or crossword puzzles, and engaging in social activities such as going out with friends. Participants then took thinking and memory tests every 15 months. Over the course of five years, 532 participants developed mild cognitive impairment.

The researchers found that using a computer in middle age was associated with a 48% lower risk of developing mild cognitive impairment and that using a computer in later life was associated with a 30% lower risk. Engaging in social activities and playing games in both middle age and later life were each associated with a 20% lower risk. Craft activities were also associated with a 42% lower risk, but only in later life.

The more activities in which people engaged during later life, the less likely they were to develop mild cognitive impairment. Engaging in two activities was associated with a 28% lower risk, engaging in three activities was associated with a 45% lower risk, engaging in four activities was associated with a 56% lower risk, and engaging in five activities was associated with a 43% lower risk.

“Persons that engage in mentally stimulating activities may have a higher likelihood of exhibiting other healthy lifestyle behaviors that may be protective against cognitive decline, such as physical activity or a healthy diet,” they wrote. “Engaging in leisure activities may also be associated with better emotional health, which in turn is associated with cognitive health.”

For related news, see the Psychiatric News article “New Insights Into How Staying Active May Delay Onset of Alzheimer’s.”

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Non-Concussive Head Impacts Not Linked to Cognitive Decline in Young Football Players, Study Finds

Youth aged 9 to 18 years who played tackle football for two seasons did not experience significant, short-term changes in cognition from repeated head impacts that did not cause a concussion, according to a study in Journal of Neurotrauma.

However, younger age and a history of attention-deficit/hyperactivity disorder (ADHD) did predict decline in cognition among the young football players. Longer-term effects are unknown and require further research.

“The study is showing us that sub-concussive impacts don't seem to be associated with changes in neurocognitive function over two seasons of youth football,” said lead author Sean Rose, M.D., a pediatric sports neurologist and co-director of the Complex Concussion Clinic at Nationwide Children's Hospital in Columbus, Ohio. “And we're finding that other factors, such as ADHD and younger age, are more predictive of worsening scores on our pre- and post-season tests.”

Rose and colleagues studied a sample of 166 youth tackle-football players over two seasons: 70 primary-school players aged 9 to 12 years and 96 high-school players aged 15 to 18 years. Sensors were placed in their helmets to record the number as well as the intensity of impacts to the head. All participants completed assessments on a variety of neurological, cognitive (including memory and attention), and behavioral outcomes before and after each football season.

In the subgroup of 55 youth who played in both seasons, neither cumulative impact nor impact intensity predicted change scores from preseason 1 to post-season 2 on any outcome measure. However, younger age did predict worse outcomes in some measures, though these changes were independent of head impacts. Also, a history of ADHD was associated with reduced scores on several cognitive measures and an ADHD symptom self-reporting scale.

“When trying to determine the effects of repeated, sub-concussive head impacts, prospective outcomes studies are an important addition to the existing retrospective studies,” said Rose in a prepared statement. “We designed this study to include a wide variety of neurocognitive outcomes tests to give us new insights into how repeated hits might influence outcomes.”

Despite the study findings, Rose said the longer-term effects of repeated impacts from tackle football on young people’s brains is unknown “We remain concerned about repetitive head impacts in children, and longer follow-up times are necessary to look for delayed effects on neurocognition,” he said.

>For related information, see the Psychiatric News article “Age When Football Hits Began May Determine Future Cognitive Problems.”

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CBT Program Reduces Addictive Internet Behaviors in Men, Study Finds

A 15-week treatment program that incorporates principles of cognitive-behavioral therapy (CBT) is effective at reducing problem gaming and other addictive internet behaviors in men, according to a study published today in JAMA Psychiatry. 

“Despite the heterogeneity of the treatment group, we found that our CBT program was effective … regardless of age, comorbidity, or treatment center,” wrote Klaus Wölfling, Ph.D., of the University Medical Center of the Johannes Gutenberg-University in Mainz, Germany, and colleagues. “These findings support a unitary concept of [internet addiction] and point to the flexibility of the STICA [short-term treatment for internet and computer game addiction].”

Internet- and gaming-related addiction is an emerging concept: Internet gaming disorder is listed in the DSM-5 under conditions for further study, and gaming disorder is included in the 11th Revision of the International Classification of Diseases (ICD-11).

Wölfling and colleagues recruited 143 men (average age 26) with addictive behaviors related to the internet and gaming from outpatient psychiatry clinics at university medical centers in Germany and Austria. The problem behaviors reported by the men included online gaming (82 men), offline gaming (9 men), online pornography (23 men), and generalized internet addiction (29 men). Participants were evaluated using the Assessment of Internet and Computer Game Addiction (AICA) scale; AICA is derived from the DSM-5’s proposed criteria for internet gaming disorder but expanded to multiple online activities.

Of the participants, 72 received STICA, which teaches patients to be cognizant of why they engage in dysfunctional internet use and provides skills to help them reduce and control their use. The treatment involved 15 weekly group sessions interspersed with eight individual sessions to aid in patient motivation and monitor participants for any emergent distress. The other 71 men were placed on a wait list and received STICA after 15 weeks.

After 15 weeks, 69% of men who received STICA achieved remission of their addiction (defined as an AICA score of 7 or less) compared with 24% of men on the wait list. The STICA group also reported less time spent online on both weekends and weekdays, fewer depression symptoms, and improved social functioning. 

“The study shows that STICA can be effective in treatment of IA [internet addiction],” Wölfling and colleagues concluded. “Further trials investigating the long-term efficacy of STICA and addressing specific groups and subgroups compared with active control conditions are required.”

For related information, see the American Journal of Psychiatry article “Internet Gaming Disorder: Investigating the Clinical Relevance of a New Phenomenon.”

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‘Secret Shopper’ Study Highlights Barriers Faced By Patients Seeking Buprenorphine

Patients seeking treatment for heroin use in areas of the United States hardest hit by the opioid epidemic may experience several barriers to care when reaching out to publicly listed “buprenorphine-waivered” prescribers, according to a study published in the July issue of the Annals of Internal Medicine. Such barriers include prescribers not accepting new patients and waits of a week or more between first appointments and buprenorphine induction.

The findings were based on a “secret shopper” study, in which callers to physicians, nurse practitioners, and physician assistants listed on the Buprenorphine Practitioner Locator website posed as a patient covered by Medicaid or without insurance in the District of Columbia, Maryland, Massachusetts, New Hampshire, Ohio, and West Virginia.

“In six [jurisdictions] with the highest burden of opioid-overdose mortality in the United States, 38% to 46% of callers who reported current heroin use were denied an appointment from a buprenorphine prescriber, and only 50% to 66% of [prescribers] booking a new appointment allowed buprenorphine induction at the first visit,” wrote senior author Michael L. Barnett, M.D., M.S., of the Harvard T.H. Chan School of Public Health and Brigham and Women’s Hospital and colleagues. “Nevertheless, among those who were accepting new patients, wait times were not long, suggesting an underused capacity for buprenorphine treatment in areas with great need.”

From July to November 2018, callers attempted to contact 1,076 publicly listed buprenorphine prescribers twice, posing as a 30-year-old woman who was using heroin and seeking to start buprenorphine-naloxone treatment. During one call, scheduling staff was told the patient was covered by Medicaid; in the other, scheduling staff was told the patient was uninsured but willing to pay for care. For each prescriber, the callers made three attempts during business hours to reach a live scheduler.

From the initial sample of 1,076 prescribers in six jurisdictions, 530 were excluded for reasons such as invalid contact information, they were inactive prescribers, or they requested information such as a Medicaid number that the caller could not provide. The callers were also unable to reach a live scheduler for 77 prescribers, while 89 prescribers were reached once but not for both scenarios, resulting in a final sample of 849 contacts for 469 prescribers. The authors found that an appointment was offered in 233 of 432 contacts (54%) by the Medicaid callers and 258 of 417 (62%) by the uninsured–self-pay callers. The median wait time to the first appointment was six days for Medicaid callers and five days for uninsured–self-pay callers.

Additionally, 27% of Medicaid callers and 41% of uninsured–self-pay callers were offered an appointment with the possibility of buprenorphine prescription at the first visit. The median wait time from first contact to possible induction was eight days for Medicaid callers and seven days for uninsured–self-pay callers.

The researchers noted several limitations of the study, including callers’ focus on publicly listed buprenorphine prescribers in five states and the District of Columbia, which limits the generalizability of the findings.

Nonetheless, Barnett and colleagues concluded, “[E]very day without treatment carries an elevated risk for escalating opioid use and overdose. Patients must be in active opioid withdrawal to initiate buprenorphine treatment safely, which makes the timing of induction critical.”

For related information, see the Psychiatric News article “What Psychiatrists Can Do to Address the U.S. Opioid Crisis.”

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Cognitive Decline After Onset of Psychosis Varies Across Cognitive Functions

Patients with schizophrenia and related psychotic disorders continue to experience cognitive decline for years after illness onset, according to a study in AJP in Advance.

“While large deficits in processing speed are already apparent at the first episode [of psychosis], deficits in verbal knowledge and memory continue to increase,” wrote Jolanta Zanelli, Ph.D., of King’s College London and colleagues. Understanding these differences can help guide cognitive remediation therapy in patients, the authors noted.

These findings were based on data collected as part of the Aetiology and Ethnicity in Schizophrenia and Other Psychoses (AESOP) study—a study that tracked changes in cognitive function in patients following a new diagnosis of psychosis. The study included 187 adults with first-episode psychosis or another psychotic disorder (for example, psychotic depression or persistent delusional disorder) who sought care in southeast London, Nottingham, or Bristol, and 177 healthy controls. All study participants were given a series of neuropsychological tests at enrollment and about 10 years later. Full 10-year data was available for 106 patients and 103 controls.

The baseline data showed that all patients with psychosis performed worse on tests measuring intellectual ability (IQ) as well as specific cognitive functions compared with controls, with patients with schizophrenia showing the greatest impairment. Approximately 10 years later, patients with schizophrenia showed worsening IQ, memory, and verbal skills compared with controls; their processing speed and visual-spatial memory did not decline. In contrast, patients with another psychotic disorder did not exhibit continued IQ decline compared with controls and only worsened in only certain memory functions.

Schizophrenia patients with severe symptoms at baseline showed greater cognitive decline over time than patients with mild or moderate symptoms; there was no evidence for an association between symptom severity and cognitive changes among patients with other psychoses. “While this subgroup was small (21% of the overall group), the magnitude of decline in the memory domain was large. Thus, this finding points to a potential subgroup of schizophrenia patients who may greatly benefit from being specifically targeted for cognitive remediation,” Zanelli and colleagues wrote.

To read more about this topic, see the Psychiatric News article “Could Cognitive Assessments Enhance Ability to Detect Transition to Psychosis?”

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Statins May Reduce Symptoms of Depression, Meta-Analysis Suggests

A class of cholesterol-lowering drugs collectively known as “statins” may improve symptoms of depression in people who have been diagnosed with the disorder, according to a meta-analysis in the Journal of Affective Disorders.

Megha S. Yatham, B.Sc., of the University of Manchester and colleagues reviewed data from 10 clinical trials of statins in which participants were randomized to at least one statin or placebo. The trials measured depressive symptoms using scales such as the Hamilton Depression Rating Scale, Beck Depression Inventory, and Geriatric Depression Scale, among others. The primary outcome was the difference in end-of-trial depression scores between participants who took statins and those who took placebo. Participants in three of the trials had been diagnosed with depression, and seven of the trials were conducted in nondepressed participants. In total, 1,348 participants received statins in the trials and 1,169 received placebo.

Yatham and colleagues found that statin use was associated with significantly lower scores on depression rating scales compared with placebo, but only among participants who had been diagnosed with depression. Although statin use was associated with improved scores in nondepressed participants as well, this difference was not enough for the researchers to consider the improvement statistically significant.

“Although the exact mechanisms by which statins might improve depressive symptoms is unknown, the leading theory is that statins decrease the inflammation and oxidative stress reported to be commonly associated with depression,” the researchers wrote. “While the results of the current meta-analysis are very promising and supportive of [the] benefits of statin therapy, further research and trials with larger sample sizes need to be conducted in order to fully explore the benefits of statins in depressed and nondepressed populations.”

For related news, see the American Journal of Psychiatry article “The Effect of Concomitant Treatment With SSRIs and Statins: A Population-Based Study.”

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Patients on Isotretinoin Should Get Regular Psychiatric Screenings, Study Suggests

Patients who take isotretinoin for severe acne may be vulnerable to several psychiatric conditions, according to a study published today in JAMA Dermatology. Specifically, depressive disorders, anxiety disorders, and mood swings were among the most common psychiatric adverse events in patients taking isotretinoin reported to the Food and Drug Administration (FDA) over a 20-year period.

Although previous studies and media reports have highlighted an association between suicidality and depression in patients taking isotretinoin, “our results suggest that other, underappreciated psychiatric adverse events may be linked to its use,” wrote senior author Arash Mostaghimi, M.D., M.P.A., M.P.H., of Brigham and Women’s Hospital, and colleagues. The findings suggest the importance of incorporating regular psychiatric screenings as part of follow-up care of patients taking isotretinoin, they noted.

The researchers analyzed reports of 17,829 psychiatric adverse events with isotretinoin as the primary suspect drug in the FDA’s Adverse Event Reporting System from 1997 through 2017. There were 7,547 reports of depressive disorders (42.3% of all adverse event reports); 2,962 reports of emotional lability, such as mood swings and irritability (16.6%); and 2,412 reports of anxiety disorders (13.5%). Additionally, there were 2,278 reports of suicidal ideation, 602 reports of attempted suicide, and 368 reports of completed suicide. Among the 13,553 adverse events that reported patient age, more than half occurred in patients aged 10 to 19.

Additional analysis of suicide data from patients enrolled in an isotretinoin risk-management program known as iPLEDGE in 2009 and 2010 revealed rates of completed suicide per 100,000 persons were 8.4 in 2009 and 5.6 in 2010. (iPLEDGE requires patients meet with physicians monthly to confirm medication is being taken correctly.) The authors noted that these rates were lower than the national suicide rates in the general population and in those aged 15 to 24 during those years.

“Although no causal link has been established between isotretinoin and psychiatric adverse events, it is important to recognize that there are data that suggest patients using this drug may be vulnerable to a number of psychiatric conditions,” the authors wrote. “Mandated monthly visits under the current iPLEDGE infrastructure may provide an opportunity to screen patients for psychiatric conditions and improve patient outcomes.”

For related news, see the Psychiatric News article “Psychiatrists Work to Tease Apart Psychosomatic Aspects of Skin Disease.”

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